POS0182 RISK-BENEFIT ASSESSMENT OF THE USE OF RITUXIMAB FOR RHEUMATOID ARTHRITIS IN REAL LIFE: FINDINGS FROM 1984 PATIENTS FROM THE FRENCH AUTOIMMUNITY AND RITUXIMAB REGISTRY
Authors: Y. Nguyen, X. Mariette, J. E. Gottenberg, M. Iudici, J. Morel, O. Vittecoq, A. Constantin, R. M. Flipo, T. Schaeverbeke, J. Sibilia, P. Ravaud, R. Porcher, R. Seror
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Most randomized clinical trials (RCTs) are explanatory studies examining whether a therapy can work under ideal circumstances. Rituximab (RTX) has been approved for treatment of rheumatoid arthritis (RA) following the results of three RCTs [1–3], including about 1000 patients. However, less than 10% of real-life patients was found to be eligible to these registration trials, because of restrictive inclusion criteria or exclusion criteria such as co-morbidities or undesired co-medication, which questions external validity of these RCTs. Whether the efficacy, tolerance or safety data obtained in highly selected RCTs patients can be extrapolated to a more heterogeneous sample of patients receiving RTX in daily practice, remains to be elucidated. <h3>Objectives</h3> We aimed to identify the main reasons limiting the eligibility of routine care patients in RTX-registration RCTs, and to investigate the relationships between the number of eligibility (both inclusion and exclusion) criteria and RTX efficacy and safety in a real-life scenario. <h3>Methods</h3> The AIR registry is a French nationwide, multicentre, prospective cohort study aiming at investigating efficacy and safety of RTX in a real-life setting. We retrieved eligibility criteria of the drug-registration trials evaluating rituximab for RA and applied them to our population. We compared the EULAR response (moderate-to-good) at 12 months and the incidence of serious adverse events (AEs, including severe infections, malignancies, major adverse cardiovascular events, and death) at 12 months between eligible and non-eligible patients. We modelized the risk-benefit ratios according to the number of fulfilled critical eligibility, defined by those associated with response and severe AEs, respectively, after backward stepwise variable elimination. <h3>Results</h3> Among 1989 RA patients included in the AIR registry, only 9 to 12% fulfilled all main eligibility criteria for the 3 drug-registration trials. The main unfulfilled inclusion criteria were an elevated CRP or ESR level (67.5%), erosive changes on bone X-ray (68.1%), and a swollen joints count ≥4/28 (74.6%). The main exclusion reasons were a history of severe or recurrent infection (35%), another severe uncontrolled disease (16%), neoplasia (14%), a high prednisone dose (≥ 10 mg/day for 26%), the use of another DMARD than methotrexate (16%) and ACR functional class IV disease (15%). Compared with RCT-eligible patients, non-eligible patients had less frequently moderate-to-good EULAR response (40.3% versus 46.9%, P=0.044), and had a smaller change in DAS-28 (-1.2 vs -1.4; 95% CI 0.1 to 0.5; P=0.005) at 12 months. Compared to patients with no exclusion criterion, patients with at least one critical exclusion criterion had a higher risk of severe AEs (HR 3.03, 95% CI 2.25–4.06 for ≥ 3 exclusion criteria compared to none). While the probability of EULAR response decreased with the number of unmet critical inclusion criteria, the probability of severe AEs increased with the number of exclusion criteria (Figure 1), highly decreasing the incremental risk-benefit ratio. <h3>Conclusion</h3> Few RA patients treated with rituximab fulfilled the eligibility criteria of the main drug-registration trials. Non-eligible patients had less chance of treatment response, and a higher risk of severe adverse events. This suggests that the efficacy and safety data from those trials cannot be extrapolated to RA patients in daily practice. <h3>References</h3> [1]Edwards et <i>al</i>. <i>N Engl J Med</i> 2004 [2]Emery P <i>et al. Arthritis Rheum</i> 2006 [3]Cohen SB <i>et al. Arthritis Rheum</i> 2006 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.